This proposal seeks to elucidate the role that proteolytic enzymes might play in the ability of tumors to invade normal tissue and to metastasize to other organs of the body, and has as its ultimate objective the design of specific inhibitors which will suppress malignant growth. In order to accomplish this objective, the following approaches will be taken: 1) to isolate clones of tumor cells (a methylcholanthrene-induced murine fibrosarcoma) which exhibit different degrees of metastatic potential and to see if there is any relationship between the latter property and the activities of various proteolytic enzymes, 2) to isolate and characterize those enzymes whose activities appear to correlate with metastatic potential. 3) to test the effectiveness of various synthetic inhibitors of these enzymes in curtailing the growth and invasive and metastatic properties of these tumors, 4) to conduct a detailed biochemical and cytogenetic analysis of the tumor cell population during multiple cycles of metastasis.